QUILT-3.067: NANT Triple Negative Breast Cancer (TNBC) Vaccine: Molecularly Informed Integrated Immunotherapy in Subjects With TNBC Who Have Progressed on or After Standard-of-care Therapy.

Phase 1

Terminated

• Conditions: Triple Negative Breast Cancer
• Interventions: Drug: Aldoxorubicin HCl; Biological: N-803; Biological: ETBX-011; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-4000; Biological: GI-6207; Biological: GI-6301; Biological: haNK for Infusion; Biological: avelumab; Biological: bevacizumab; Drug: Capecitabine; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: nab-Paclitaxel; Procedure: SBRT

• Registration Number: NCT03387085
• Lead Sponsor: ImmunityBio, Inc.

Brief Summary

This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with TNBC who have progressed on or after previous SoC chemotherapy. Phase 2 will be based on Simon's two-stage optimal design.

Detailed Description

Treatment will be administered in two phases, an induction and a maintenance phase, as described below. Subjects will continue induction treatment for up to 1 year. Treatment in the study will be discontinued if the subject experiences progressive disease (PD) or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) in the induction phase will enter the maintenance phase of the study. Subjects who experience ongoing stable disease (SD) or an ongoing partial response (PR) at 1 year may enter the maintenance phase at the Investigator's discretion. Subjects may remain on the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. The maximum time on study treatment, including both the induction and maintenance phases, is 2 years.

Study Timeline

• Study First Submitted: 2017-12-21
• Study First Submitted QC: 2017-12-21
• Study First Posted: 2017-12-29
• Study Start: 2018-03-19
• Primary Completion: 2020-09-11
• Study Completion: 2024-01-16
• Results First Submitted: 2024-04-03
• Status Verified: 2024-08
• Results First Submitted QC: 2024-08-05
• Last Update Submitted: 2024-08-05
• Results First Posted: 2024-08-09
• Last Update Posted: 2024-08-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

1. Age ≥ 18 years old.
2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
3. Histologically-confirmed metastatic or unresectable TNBC that has either progressed on or after anthracycline-based chemotherapy (or other approved standard of care therapy) or subject has refused anthracycline-based chemotherapy, or other taxane- and platinum-based therapies. TNBC is defined as breast cancer that lacks estrogen receptor (ER) and progesterone receptor (PR) expression, and human epidermal growth factor receptor 2 (HER2) overexpression and/or amplification.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Have at least 1 measurable lesion of ≥ 1.0 cm.
6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen following the conclusion of the most recent anticancer treatment. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period, if considered safe by the Investigator. If safety concerns preclude collection of a biopsy during the screening period, a tumor biopsy specimen collected prior to the conclusion of the most recent anticancer treatment may be used.
7. Must be willing to provide blood samples prior to the start of treatment on this study.
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment, if considered safe by the Investigator.
9. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
10. Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence.

Exclusion Criteria

1. Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.

2. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).

3. History of organ transplant requiring immunosuppression.

4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

5. Inadequate organ function, evidenced by the following laboratory results:

   1. Absolute neutrophil count < 1000 cells/mm3.
   2. Platelet count < 75,000 cells/mm3.
   3. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL).
   4. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
   5. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
   6. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
   7. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
   8. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3.

6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication. Subjects with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry.

7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (LVEF) 10% below the institution's lower limit of predicted normal.

8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.

9. Positive results of screening test for human immunodeficiency virus (HIV).

10. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.

11. Known hypersensitivity to any component of the study medication(s).

12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.

13. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study day 1.

14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.

15. Participation in an investigational drug study or history of receiving any investigational treatment within 30 days prior to initiation of treatment on this study, except for testosterone-lowering therapy in men with prostate cancer.

16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

17. Concurrent participation in any interventional clinical trial.

18. Pregnant and nursing women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NANT triple negative breast cancer (TNBC) Vaccine	ETBX-051	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	N-803	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	ETBX-011	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	ETBX-061	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	GI-4000	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	GI-6207	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	GI-6301	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	haNK for Infusion	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	avelumab	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	bevacizumab	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	Capecitabine	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	SBRT	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	Aldoxorubicin HCl	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	nab-Paclitaxel	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	Cisplatin	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	Cyclophosphamide	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	5-Fluorouracil	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.
NANT triple negative breast cancer (TNBC) Vaccine	Leucovorin	A combination of agents will be administered to subjects in this study: Aldoxorubicin HCl, N-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, SBRT.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)	Up to 2 years	Graded using the NCI CTCAE Version 4.03.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate by RECIST v1.1	Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression. Up to 2.5 years	Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT) or magnetic resonance imaging (MRI) of target and non-target lesions in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Percent of subjects with confirmed complete Response (CR; disappearance of all target lesions) or partial response (PR; \>=30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum diameters.
Objective Response Rate by irRC (Percent of Subjects With Confirmed Complete or Partial Overall Response)	Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression. Up to 2.5 years.	Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT) or magnetic resonance imaging (MRI) of target and non-target lesions in accordance with Response Evaluation Criteria in Solid Tumors (irRC) Version 1.1. Percent of subjects with confirmed complete Response or partial response by irRC.
Progression Free Survival by RECIST v1.1	Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first. Up to 2.5 years.	PFS were defined as the time from the date of first treatment to the date of disease progression or death (any cause), whichever occured first. Subjects completing study follow-up or starting a new anticancer therapy prior to documented PD were censored in the PFS analysis at the last known date the subject was progression free prior to completing follow-up or initiating new therapy.
Progression Free Survival by irRC	Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first.	PFS were defined as the time from the date of first treatment to the date of disease progression or death (any cause), whichever occured first. Subjects completing study follow-up or starting a new anticancer therapy prior to documented PD were censored in the PFS analysis at the last known date the subject was progression free prior to completing follow-up or initiating new therapy.
Duration of Response by RECIST Version 1.1	Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first.	DOR were evaluated using Kaplan-Meier methods for those subjects with a confirmed response. DOR were defined as the time from the date of first response (PR or CR) to the date of disease progression or death (any cause) whichever occured first. Responding subjects completing study follow-up or starting a new anticancer therapy prior to documented PD were censored in DOR analysis at the last known date the subject was progression free prior to completing follow-up or initiating new therapy.
Disease Control Rate by RECIST Version 1.1	Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression. Up to 2.5 years.	Disease control was defined as subjects with a confirmed Complete Response (CR), Partial Response (PR), or Stable Disease (SD) lasting for at least 2 months.; Complete response (CR; disappearance of all target lesions) or partial response (PR; \>=30% decrease in the sum of the longest diameter of target lesions) or stable disease (SD; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD)
Duration of Response by irRC	Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first.	DOR were evaluated using Kaplan-Meier methods for those subjects with a confirmed response. DOR were defined as the time from the date of first response (PR or CR) to the date of disease progression or death (any cause) whichever occured first. Responding subjects completing study follow-up or starting a new anticancer therapy prior to documented PD were censored in DOR analysis at the last known date the subject was progression free prior to completing follow-up or initiating new therapy.
Disease Control Rate by irRC	Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first. Up to 2.5 years.	Disease control was defined as subjects with a confirmed Complete Response (irCR), Partial Response (irPR), or Stable Disease (irSD) lasting for at least 2 months.; Complete response (irCR; disappearance of all index lesions) or partial response (irPR; \>=100% decrease in the sum of the longest diameter of index lesions with stable non-index lesions or \>=50% decrease in the sum of index lesions with absent/stable /progressed non-index lesions) or stable disease (irSD; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD)
Overall Survival	Evaluated from screening to death.	OS were evaluated using Kaplan-Meier methods. OS were defined as the time from the date of first treatment to the date of death (any cause). Subjects who are alive at the end of follow-up were censored in the OS analysis at the last known date alive.
Quality of Life by Patient Reported Outcomes	Up to 2.5 years	Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) instrument on study

Trial Locations

Locations (1)

Chan Soon-Shiong Institute for Medicine; 🇺🇸 El Segundo, California, United States